A randomized phase II study of Pembrolizumab (MK-3475) as maintainance therapy in patients with unresectable stage III non-small cell lung cancer treated with definitive chemo-radiotherapy (MP-LALC- Maintainance Pembrolizumab in Locally Advanced Lung Cancer).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita' Degli Studi Di Torino

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514701-57-01

EudraCT number

2016-001252-22

ClinicalTrials.gov

NCT03379441

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective is to evaluate if treatment with chemo-radiotherapy
followed by Pembrolizumab (MK-3475) maintenance (up to 24 months) results in
superior Overall Survival (OS) in stage IIIA-B, unresectable, NSCLC compared to
chemo-radiotherapy (CT-RT) followed by observation

Secondary objectives 3

1. To evaluate Rate (%) of patients without disease progression at 12, 18 and 24 month
2. To evaluate acute and chronic toxicity in stage IIIA-B, unresectable NSCLC who receive Pembrolizumab after CT-RT.
3. To evaluate programmed death-ligand 1 (PD-L1) expression in locally advanced NSCLC, at baseline and after chemo-radiotherapy

Conditions and MedDRA coding

non Small Cell Lung Cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Be willing and able to provide written informed consent/assent for the trial.
2. Be 18 years of age on day of signing informed consent.
3. Have measurable disease based on RECIST 1.1
4. Be willing to provide tissue from a newly obtained core, trucut biopsy or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newlyobtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the PI
5. Have a performance status of 0 or 1 on the ECOG Performance Scale
6. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation
7. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
8. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Section 8.14.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
9. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion criteria 16

1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatmen
3. Has a known history of active Bacillus Tuberculosis (TB)
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
7. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
8. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or has evidence of interstitial lung disease
9. Has an active infection requiring systemic therapy.
10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
12. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
13. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
15. Has known active Hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or Hepatitis C (e.g., HCV ribonucleic acid [RNA] qualitative is detected).
16. Has received a live vaccine within 30 days of planned start of study therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Median overall survival (OS) time

Secondary endpoints 3

1. Overall survival (OS) defined as the time from randomization to death or last follow-up
2. Progression Free Survival (PFS) intended as the time from randomization to disease progression or death
3. Overall Response Rate (ORR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita' Degli Studi Di Torino

Sponsor organisation

Universita' Degli Studi Di Torino

Address

Regione Gonzole 10

City

Orbassano

Postcode

10043

Country

Italy

Scientific contact point

Organisation

Universita' Degli Studi Di Torino

Contact name

Francesco Passiglia

Public contact point

Organisation

Universita' Degli Studi Di Torino

Contact name

Francesco Passiglia

Third parties 1

Sponsor responsibilities

Article 77 compliance

Universita' Degli Studi Di Torino

Contact point sponsor

Universita' Degli Studi Di Torino

Article 77 implementation

Universita' Degli Studi Di Torino

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications